title: Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies.
abstract: A HIV-1 tier system has been developed to categorize the various subtype viruses based on their sensitivity to vaccine-induced neutralizing antibodies (NAbs): tier 1 with greatest sensitivity, tier 2 being moderately sensitive, and tier 3 being the least sensitive to NAbs (Mascola et al., J Virol 2005; 79:10103-7). Here, we define an FIV tier system using two related FIV dual-subtype (A+D) vaccines: the commercially available inactivated infected-cell vaccine (Fel-O-Vax(®) FIV) and its prototype vaccine solely composed of inactivated whole viruses. Both vaccines afforded combined protection rates of 100% against subtype-A tier-1 FIVPet, 89% against subtype-B tier-3 FIVFC1, 61% against recombinant subtype-A/B tier-2 FIVBang, 62% against recombinant subtype-F'/C tier-3 FIVNZ1, and 40% against subtype-A tier-2 FIVUK8 in short-duration (37-41 weeks) studies. In long-duration (76-80 weeks) studies, the commercial vaccine afforded a combined protection rate of at least 46% against the tier-2 and tier-3 viruses. Notably, protection rates observed here are far better than recently reported HIV-1 vaccine trials (Sanou et al., The Open AIDS J 2012; 6:246-60). Prototype vaccine protection against two tier-3 and one tier-2 viruses was more effective than commercial vaccine. Such protection did not correlate with the presence of vaccine-induced NAbs to challenge viruses. This is the first large-scale (228 laboratory cats) study characterizing short- and long-duration efficacies of dual-subtype FIV vaccines against heterologous subtype and recombinant viruses, as well as FIV tiers based on in vitro NAb analysis and in vivo passive-transfer studies. These studies demonstrate that not all vaccine protection is mediated by vaccine-induced NAbs.
authors.affiliation: Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA.
authors.forename: James K
authors.initials: JK
authors.lastname: Coleman
authors.affiliation: Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA.
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Pu
authors.affiliation: Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA.
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Martin
authors.affiliation: Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA.
authors.forename: Ezra N
authors.initials: EN
authors.lastname: Noon-Song
authors.affiliation: MSD Animal Health, 54-68 Ferndell Street, South-Granville, NSW 2142, Australia.
authors.forename: Raphael
authors.initials: R
authors.lastname: Zwijnenberg
authors.affiliation: Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA. Electronic address: yamamoto@ufl.edu.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D002415:Cats; D056738:Cross Protection; D016181:Feline Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D007116:Immunization, Passive; D016089:Immunodeficiency Virus, Feline / Q000145:classification; D015164:Vaccines, Inactivated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines
keywords: Efficacy; FIV; HIV-1; Neutralizing antibody tiers; Passive transfer; Vaccine